Production of s-ammonium phosphoric acid esters and thiolo-phosphoric acid esters from thiono-phosphoric acid esters

ABSTRACT

The sulfur moiety of a thiono-phosphoric acid ester is converted to the S-ammonium salt by reacting the thionophosphoric acid ester with an ammonium sulfide or polysulfide. The S-ammonium salt may be alkylated to produce the thiolophosphoric acid ester.

United States Patent [1 1 F ranke PRODUCTION OF S-AMMONIUM PI-IOSPHORICACID ESTERS AND THIOLO-PHOSPHORIC ACID ESTERS FROM THIONO-PHOSPHORICACID ESTERS [75] Inventor: Hans G. Franke, Orinda, Califv [73] Assignee:Chevron Research Company, San Francisco, Calif.

[ Notice: The portion of the term of this patent subsequent to Aug. I3,1991, has been disclaimed.

[22] Filed: Sept. 24, 1973 [21] Appl. No.: 400,288

Related US. Application Data [63] Continuation-impart of Ser. No.317,479, Dec. 21,

I972 Pat. No. 3,832,425.

[52] US. Cl. 260/987; 260/978; 260/979 [51] Int. Cl. C07F 9/24; CO7F9/165 [58] Field of Search 260/987 [56] References Cited UNITED STATESPATENTS 3.831425 8/1974 Franke 260/987 x Primary Examiner-Anton H. SuttoAttorney, Agent, or Firm-J. A. Buchanan, Jr.; John Stoner, J r.; RaymondOwyang [57] ABSTRACT 7 Claims, N0 Drawings RELATED APPLICATION Thisapplication is a continuation-in-part of application Ser. No. 317,479,filed Dec. 21, 1972, now US. Pat. No. 3,832,425.

BACKGROUND OF THE INVENTION The sulfur-containing derivatives oforthophosphoric acid esters exist in two isomeric forms (1, thiono, andII,

thiolo).

i ii A A PR P-S-R B B (I) (II) SUMMARY OF THE INVENTION It has now beenfound that the thiono form ofa phosphoric acid ester can be converted tothe thiolo form by: (1) reacting a thiono-phosphoric acid ester withammonium sulfide or polysulfide to form an S- ammonium salt; and (2)alkylating the S-ammonium salt to form the sulfur ester (thiolo form) ofthe phosphoric acid ester.

DESCRIPTION OF THE INVENTION The process of the invention may beillustrated by the following equations:

I A (l) RO-P (2) NI-LS- m-nx wherein A, B and R represent organo groupsand RX represents an alkylating agent, e.g., methyl iodide.

In general, the process of the invention is suitable for the conversionof any thiono-phosphoric acid ester compound to a thiolo-phosphoric acidester The term thiono-phosphoric acid ester," as employed in thisspecification, means a pentavalent phosphorus acid ester having thefollowing partial structure:

2 wherein R is an organo group and the dangling valences are satisfiedby suitable organo group(s) or amino. The term thiolophosphoric acid"therefore refers to the corresponding sulfur ester, Let,

Examples of suitable thiono-phosphoric acid ester reactants aretabulated in Table I. All of the thionophosphoric acid esters are known,and most are disclosed in Chemical Week, June 21, 1972, pp. 34-66, andJuly 26, 1972, pp. 18-46.

TABLE I 0,0,0',O'-tetramcthyl-(),O-thiodi-p-phenylenephosphorothioate2-(0,0-diethylthionophosphoryl)-5-methyl-6-carbethoxypyrazolo-(1,5a)-pyrimidineO-[2-chloro-1-(2,5-dichlorophenyl)-vinyl]-0,0-die' thylphosphorothioate0,0,0,0-tetrapropyldithiopyrophosphateS-(0,0-diisopropylphosphorodithioate) ester of N-(2-mercaptoethyl)benzenesulfonamide0,0-diethyl-O-3-chloro-4-methyl-2-oxo-2H- l -benzopyran-7-yl-phosphorothioate O-p-cyanophenyl-0,0-dimethylphosphorothioate0,0-diethyl-O-(2-isopropyl6-methyl-4-pyrimidinyl)- phosphorothioate0,0-dimethyl-S-(N-methylcarbamoylmethyl)-phosphorodithioate2,3-p-dioxanedithiol-S,S-bis-(0,0diethylphosphorodithioate)0,0-diethyl-S-[2-(ethylthio)-ethyl]-phosphorodithioate0,0-diethyl-O-(3,5,6-trichloro-2-pyridyl)-ph0sphorothioateO-ethyl-S-phenyl-ethylphosphonodithioateO-ethyl-O-p-nitrophenylphenylphosphonothioate0,0,0',O'-tetraethyl-S-S'-methylenebisphosphorodithioate0,0-dimethyl-O[4-methylthio)-m-tolyll-phosphorothioate0,0-diethyl-O-[p-(methylsulfinyl)-phenyl]-phosphorothioate0,0-bis-(p-chlorophenyl)-acetimidoylphosphoramidothioate0,0-diethyl-s-[4-oxo-1,2,3-benzotriazin-3-(4H)-ylmethyl]phosphorodithioate 1-phenyl-3-(0,0-diethylthionophosphoryl)-1,2,4-

triazol. N-(mercaptomethyl)phthalimide-S-(0,0-dimethylphosphorodithioate0,0-dimethylphosphorodithioate of diethyl mercaptosuccinateS-(4,6-diamino-s-triazin-2-ylmethyl)-0,0-dimethyl phosphorodithioate0,0-dimethyl-O-p-nitrophenylphosphorothioate0,0-diethyl-O-p-nitrophenylphosphorothioate0,0-dimethyl-S-(a-ethoxycarbonylbenzyl)phosphorodithioate0,0-diethyl-S-(ethylthio)-methylphosphorodithioateO-(4-bromo-2,5-dichlorophenyl)-O-methylphenylphosphonothioate2-diethylamino-6-methylpyrimidin-4-yl-diethylphosphorothioate 30,0-dimethyl-O-(2,4,5-trichlorophenyl)phosphorothioate 2-methoxy-4H- l,3,Z-benzodioxaphosphorin-2-sulfide0,0-dimethyl-O-(4-nitro-m-tolyl)-phosphorothioate0,0-dimethyl-S-(2-methoxy-l,3,4-thiadiazol-5-(4H)-onyl-4-methylphosphorodithioateO-p-cyanophenyl-O-ethylphenylphosphonothioate0,0-diethyl-O-[2-(ethylthio)-ethyl] phosphorothioate S-( Z-chlorol-phthalimido-ethyl )-0,0-diethylphosphorodithioate S-[ {(p-chlorophenyl)thio}methyl ]-0,0-diethylphosphorodithioate-2,4-dichlorophenyl-0,0-diethylphosphorothioate0,0'diethyl-O-(2-pyrazinyl)phosphorothioate0,0-diethyl-S-[(6-chloro-2-oxobenzoxazolin-3-yl methyl]phosphorodithioate0,0-dimethyl-S-2-(acetylaminoethyl)phosphorodithioate0,0-dimethyl-S-(Z-methoxyethylcarbamoylmethyl)- phosphorodithioateBis(dialkylphosphinothioyl) disulfide0,0-diethyl-O-2,4-dichlorophenylphosphorothioate0,0-dimethylphosphoroamidothioateO-methyl-O(4-chloro-2-nitrophenyl)-N-isopropylphosphoroamidothioateO-ethyl-O-( 4-methylthiophenyl)-S-( 2-phenylethyl)- phosphorodithioate0,0-dimethyl-S-(2-ethylthioethyl )phosphorodithioate0,0-dimethyl-S-(2-phenylethy])phosphorodithioate0,0-dimethyl-S-benzylphosphorodithioateO-methyl-N,N-di-(dimethylamino)phosphoroamidothioate Two preferredclasses of thiono-phosphoric acid ester reactants are represented byformulas (Ill) and (IV):

wherein R is lower alkyl of l to 6 carbon atoms or alkenyl of 3 to 6carbon atoms, Y is oxygen or sulfur and R is R, monocyclic aryl (phenyl,phenylalkyl or alkylphenyl) of up to carbon atoms and up to 3 fluorine,chlorine, bromine, nitro, cyano, alkoxy of 1 to 4 carbon atoms, oralkylthio of l to 4 carbon atoms, and X is YR, amino, N-alkylamino of lto 6 carbon atoms, N,N-dialkylamino of 2 to 10 carbon atoms or N-alkanoylamido (i.e.,

wherein R is alkyl of l to 9 carbon atoms) of 2 to 10 carbon atoms.

Representative alkyl groups which R and R may represent include methyl,ethyl, propyl, isopropyl, butyl, secpentyl and hexyl. Representativealkenyl groups which R and R may represent include allyl, Z-butenyl,3-butenyl 2-hexenyl, S-hexenyl, etc. Representative phenylalkyl R groupsare benzyl, 2-phenylethyl, 3-(0- tolyl)propyl, 4-phenylhexyl,6-(o-t0ly])hexyl, etc. Representative alkylphenyl R groups are o-tolyl,p-tolyl, 2,4-dimethylphenyl, 3,5-diisopropylphenyl, 4-t-butylphenyl,etc. Representative substituted-aryl R groups include Z-fluorophenyl,4-chlorophenyl, 2,4- dichlorophenyl, 4-nitrophenyl,3-methyl-4-nitrophenyl, 3-methoxyphenyl, 4-cyanophenyl,Z-methylthiophenyl, 4-chlorobenzyl, 2-chloro-4-methylphenyl, etc.Representative X groups wherein X is YR are methoxy, methylthio,2-propenyloxy, phenoxy, phenylthio, 4- chlorophenoxy, benzyloxy,benzylthio, 2-nitro-4- methylphenoxy, 3-methoxy-4-chloro-Z-tolylthio,etc. Representative N-alkylamino X groups are methylamino, ethylamino,n-propylamino and isopropylamino, and representative N,N-dialkylamino Xgroups are dimethylamino, diethylamino and methylethylamino.Representative N-alkanoylamido X groups are N-acetylamido,N-propionylamido, Nhexanoylamido, etc.

The preferred R groups are alkyl, especially methyl or ethyl. Thepreferred Y group is oxygen, and the preferred R groups are alkyl. Thepreferred X groups are YR wherein R is phenyl or phenyl substituted withhalogens, nitro, cyano, alkoxy of l to 4 carbon atoms or alkylthio of lto 4 carbon atoms, and amino, N- alkylarnino and N,N-dialkylarnino. Themost preferred X groups are amino, N-alkylamino and N,N-dialkylamino.

As defined in this specification, thiono-phosphoric acid esters may haveone O-ester moiety, e.g.,

two O-ester moieties, e.g.,

or three O-ester moieties, e.g.,

if the thiono-phosphoric acid ester contains two or three O-estermoieties, then during reaction of the thiono-phosphoric acid ester withammonium sulfide or polysulfide the oxygen atom of any one of theO-ester moieties may be converted to the oxygen atom doublebonded tophosphorus (i.e., the P=O oxygen). However, a P-O-alkyl ester moiety isgenerally preferentially converted to the P=O oxygen, unless the organogroup bonded to the oxygen atom (e.g., R) is a moiety which forms arelatively stable carbonium ion, e.g., CH3CHg CH2 OI C HgCHz.

Ammonium sulfide and polysulfide, e.g. (NH ),S,, wherein X is 1 to 5, ofreasonable purity, are suitably employed for the preparation of theS-ammonium salt. Commercially available aqueous solutions of ammoniumsulfide or polysulfide are particularly suitable for use.

The reaction of the ammonium sulfide or polysulfide with thethiono-phosphoric acid ester is conducted in the liquid phase in thepresence or absence of an inert solvent which is liquid at reactiontemperature and pressure. Suitable organic solvents include oxygenatedhydrocarbons such as alkanols of l to 6 carbon atoms, e.g., methanol,ethanol, isopropanol, butanol, hexanol, etc.; dialkyl ketones of up to 8carbon atoms, e.g., acetone, methyl ethyl ketone, etc., acyclic alkylethers, e.g., dimethyl ether, dibutyl ether dimethoxyethane, diethyleneglycol dimethyl ether, etc.; and cycloalkyl ethers, e.g., dioxane,tetrahydrofuan and tetrahydropyran. Other suitable organic solventsinclude nitriles such as acetonitrile and propionitrile; anddialkylamides such as dimethylformamide; dialkylsulfoxides such asdimethylsulfoxide. Still other suitable solvents comprise water or watercontaining a portion of a polar organic cosolvent. Suitable mixtures ofwater and a polar organic cosolvent vary by volume, from about 20percent cosolvent to 80 percent cosolvent and from about 20 percentwater to 80 percent water. Solvents are used in quantities sufficient toform a slurry of the reactants or a substantially liquid phase solution.Generally, up to 100 mols of solvent per mol of the thionophosphoricacid ester is employed. The reaction is preferably conducted in thepresence of a solvent, and the preferred solvent is water or a mixtureof water and a polar organic solvent.

The temperature of the reaction may vary from about 10 to 100C,preferably from 25 to 75C. Pressure is not critical, as long as thereaction mixture is maintained substantially in a non-gaseous phase.Typical pressures vary from l to 10 atomospheres. The time of reactionvaries with the temperature. In general, the reaction is complete withinl hours, more usually within hours or less.

The molar ratio of ammonium sulfide or polysulfide to thiono-phosphoricacid ester varies from about 1:2 to :1, preferably from about l:2 to2:l.

The preparation of the S-ammonium salts produce as by-productshydrocarbyl mercaptans, dihydrocarbyl sulfides and/or dihydrocarbylpolysulfides, e.g., RSH, RSR or RSSR, wherein R has the samesignificance as previously defined. It has been found that theadditional presence of sulfur and/or ammonia as reaction componentsresults in the formation of principally dihydrocarbyl disulfideby-products. When sulfur or ammonia is employed, the molar ratio ofsulfur (or ammonia) to ammonium sulfide or polysulfide varies from about5:1 to lzS, preferably from about 2:1 to 1:2.

The precise method of contacting the reactants employed in thepreparation of the S-ammonium salt is not critical. In the preferredmodification, the sulfide or polysulfide, the thiono-phosphoric acidester and solvent (and sulfur or ammonia, if any) are maintained withagitation at reaction temperature and pressure for the desired reactionperiod. The S-ammonium salt of the phosphoric acid ester is sometimessoluble in the reaction medium and may be used for further reactionswithout separation. However, the product usually precipitates uponstanding as a solid crystalline material which may be collected byfiltration, centrifugation or decantation. The solid product can bepurified by washing with a liquid or by crystallization from anappropriate solvent, such as acetone, ethanol, etc.

As depicted in equation (2), ammonium salts of the phosphoric-acid esterare converted to thiolo-phosphoric acid esters by reacting the ammoniumsalt with an alkylating agent. Suitable alkylating agents include thealkyl, alkenyl and aralkyl halides of up to 10 carbon atoms, such asmethyl iodide, ethyl bromide, allyl chloride, hexyl bromide, crotylchloride, benzyl chloride,

propargyl bromide, isopropyl iodide, etc.; the dialkyl and dialkenylsulfates of up to 10 carbon atoms, such as dimethyl sulfate, diethylsulfate, diallylsulfates, etc; and the alkyl and alkenyl aryloralkenesulfonates, such as methyl p-tolune sulfonate, ethyl2,4-xylenesulfonate, allyl p-toluene sulfonate, methyl methanesulfonate,allyl methanesulfonate, etc. Other suitable alkylating agents includehaloalkanoates of up to l0 carbon atoms such as methyl bromoacetate,ethyl-4-bromobutyrate, etc. The preferred alkylating agents are alkylhalides, alkenyl halides and dialkyl sulfates.

Alkylation is effected by conventional procedures, e.g., as by reactingammonium salts of the phosphoric acid ester and the alkylating agent inan inert solvent or an excess of liquid alkylating agent at temperaturesin the range 080., preferably 2560C. Suitable solvents are thehalogenated hydrocarbons such as dichloromethane, chloroform,tetrachloroethane, or acetonitrile, acetone, methanol, etc. Thepreferred solvent is water.

EXAMPLES EXAMPLE 1 Preparation ofS-ammonium-O-methyl-phosphoroamidothioate A mixture of 35.3 g (0.25 mol)0,0-dimethylphosphoroamidothioate and 69.3 g (0.2 mol [NH ],S) of 20weight percent aqueous ammonium sulfide was heated at C. for 2 hours.The resulting yellow solution was evaporated under reduced pressure togive a yellow oil. The oil was diluted with a little dimethylformamide.After standing for several hours at about 25C., the oil crystallized togive the crude ammonium-salt product. The ammonium salt was filtered,washed with acetonitrile and dimethyl ether, and dried under vacuum overphosphorus pentoxide. A 73% yield of the ammonium salt was obtained. Thenuclear magnetic resonance spectrum showed a 3-proton doublet at 3.386,.I 14 Hz, (-OCH and a 6-proton multiplet at 4.488 (NH).

EXAMPLE 2 Preparation of O,S-dimethylphosphorodithioate of diethylmercaptosuccinate (isomalathion) A mixture of 34.7 g0,0-dimethylphosphorodithioate of diethyl mercaptosuccinate (malathion),9.95 g of 53 percent aqueous ammonium sulfide, 2.4 g sulfur flowers and40 ml water was maintained at 50C. for 2% hours under an atmosphere ofnitrogen. The resulting solution was placed in a cold-water bath. A 14.4sample of dimethyl sulfate was then added to the solution over ahalf-hour period. The organic phase of the reaction mixture wasseparated, washed with water, dried with magnesium sulfate andevaporated under reduced pressure to give the isomalathion product. Thenuclear magnetic resonance spectrum showed the SCH group as a doublet at2.388, I 15 Hz, and the OCH;, group as a doublet at 3.808, J l3 Hz.

EXAMPLE 3 Preparation ofS-ammonium-O-methyl-N-acetylphosphoroamidothioate A mixture of 0.046 mol0,0-dimcthyl-N-acetylphosphoroamidothioate, 0.05 mol ammonium sulfideand 0.7 mol water was heated at 55C. for 3 hours. The reaction mixturewas evaporated at low temperature under reduced pressure to give thecrude ammonium 7 salt product. The ammonium salt was then purified bywashing with acetonitrile. The salt had a melting point greater than220C. and a nuclear magnetic resonance spectrum having a doublet at3.558, .1 13 Hz (OCH and a doublet at 2.068, J 1 Hz (CH EXAMPLE 4Preparation of Smethyl-O-methyl-N-acetylphosphoroamidothioateS-ammonium-O-methyl-N-acetylphosphoi'oamidothioate was prepared by aprocedure similar to that of Example 3, except that the ammonium saltwas not isolated. Instead, the ammonium salt-containing reaction mixturewas acidified with sulfuric acid to pH 5.4 and then reacted with 0.26mol of dimethyl sulfate for 3 hours at -30C. The resulting reactionmixture was neutralized (pH 7) with ammonium hydroxide and then wascontinuously extracted with methylene dichloride. Evaporation of themethylene dichloride extracts gave a 93.6 percent yield ofS-methyl-O-methyl-N-acetylphosphoroamidothioate, m.p. 8285C. (a commercial insecticide marketed under the trade name OR- THENE Insecticide).

EXAMPLE 5 Preparation ofS-ammonium-O-methyl-N-acetylphosphoroamidothioate A mixture of 0.744 mol0,0-dimethyl-N-acetylphosphoroamidothioate, 0.744 mol ammoniumpolysulfide [(NHJ S wherein X is l to 5] and 11.3 mols water was heatedat 60C. for 2 hours. The reaction mixture was evaporated at lowtemperature under reduced pressure to give the ammonium salt. The saltwas then purified by washing with acetonitrile. The melting point of thesalt was greater than 220C.

EXAMPLE 6 Preparation ofS-ammonium-O-methyl-N-isopropylphosphoroamidothioate A mixture of 18.3 g(0.1 mol) QO-dimethyl-N-isopropylphosphoroamidothioate, 13.1 g (0.1 mol[NH ],S) of 52 percent aqueous ammonium sulfide, 30 ml water and 72 mlethanol was heated for about 3 hours. On standing overnight, unreactedstarting material crystallized from the reaction mixture. The reactionmixture was filtered and the filtrate was evaporated to give an aqueousslurry. The slurry was filtered, and the aqueous filtrate was evaporatedunder reduced pressure to give the crude ammonium salt product. The saltwas purified by washing with acetonitrile and dried. The nuclearmagnetic resonance spectrum showed a 3-proton doublet at 3.388, J 13 Hz,(OCH a lproton singlet at 4.52 (NH), a l-proton multiplet at 3.158(-CH), and a 6-proton doublet at 1.08, J 5 Hz, (CH

What is claimed is:

1. A process for preparing S-ammoniurn salts of thiono-phosphoric acidesters which comprises reacting a thiono-phosphoric acid ester of theformula wherein R is alkyl of 1 to 6 carbon atoms or alkenyl of 3 to 6carbon atoms, Y is oxygen or sulfur, R is alkyl or 1 to 6 carbon atomsor alkenyl of 3 to 6 carbon atoms and X is amino, N-alkylamino of 1 to 6carbon atoms, N,N-dialkylamino of 2 to 10 carbon atoms orN-alkanoylamino of 2 to 10 carbon atoms, which comprises reacting saidester with an ammonium sulfide or polysulflde in liquid phase at atemperature from about 10C. to C.

2. The process of claim 1 wherein the thiono-phosphoric acid ester is0,0-dimethylphosphoroamidothioate.

3. The process of claim 1 wherein the process is conducted in aqueoussolution.

4. The process of claim 1 wherein 0.2 to 5 mols of sulfur per mol ofsulfide or polysulfide is employed as an additional reactant.

5. A process for preparing the S-ammonium salt of malathion whichcomprises reacting malathion with an ammonium sulfide or polysulfide inliquid phase at a temperature from about 10C. to 100C.

6. The process of claim 5 wherein the process is conducted in aqueoussolution.

7. The process of claim 5 wherein 0.2 to 5 mols of sulfur per mol ofsulfide or polysulfide is employed as an additional reactant.

* :r s It:

1. A PROCESS FOR PREPARING S-AMMONIUM SALTS THIONOPHOSPHORIC ACID ESTERSWHICH COMPRISES REACTING A THIONOPHOSPHORIC ACID ESTER OF THE FORMULA 2.The process of claim 1 wherein the thiono-phosphoric acid ester isO,O-dimethylphosphoroamidothioate.
 3. The process of claim 1 wherein theprocess is conducted in aqueous solution.
 4. The process of claim 1wherein 0.2 to 5 mols of sulfur per mol of sulfide or polysulfide isemployed as an additional reactant.
 5. A process for preparing theS-ammonium salt of malathion which comprises reacting malathion with anammonium sulfide or polysulfide in liquid phase at a temperature fromabout 10*C. to 100*C.
 6. The process of claim 5 wherein the process isconducted In aqueous solution.
 7. The process of claim 5 wherein 0.2 to5 mols of sulfur per mol of sulfide or polysulfide is employed as anadditional reactant.